Design and evaluation of Peptide amphiphiles with different hydrophobic blocks for simultaneous delivery of drugs and genes

Macromol Rapid Commun. 2010 Jul 1;31(13):1212-7. doi: 10.1002/marc.200900935. Epub 2010 Jun 22.


In this study, peptides with six different compositions were designed and synthesized to study the effect of the structure of the hydrophobic block in triblock oligopeptide amphiphiles ((A(m) X)(n) H(5) K(15) ) on self-assembly properties, drug loading capacity and gene expression efficiency. The peptides were synthesized using a standard Fmoc-solid phase peptide synthesis protocol, which are A(12) H(5) K(15) , A(11) FH(5) K(15) , (A(5) F)(2) H(5) K(15) , (A(3) F)(3) H(5) K(15) , (AF)(6) H(5) K(15) and (AL)(6) H(5) K(15) . A(12) H(5) K(15) , A(11) FH(5) K(15) , (A(5) F)(2) H(5) K(15) and (A(3) F)(3) H(5) K(15) , formed micelles at concentrations above 200 mg · L(-1) with large size or aggregation. However, (AF)(6) H(5) K(15) and (AL)(6) H(5) K(15) had CMC values of 42 and 49 mg · L(-1) respectively, and the resulting micelles were much smaller in size as compared to the other peptide designs (108 and 233 nm for (AF)(6) H(5) K(15) and (AL)(6) H(5) K(15) , respectively). In addition, both peptides were able to load paclitaxel (PTX) into nanoparticles although PTX-loaded (AF)(6) H(5) K(15) nanoparticles had a smaller size (278 versus 295 nm, respectively). Encapsulation efficiency of PTX with (AF)(6) H(5) K(15) nanoparticles was 74%. Gene transfection studies showed that luciferase expression level induced by (AF)(6) H(5) K(15) micelles in HepG2 cell line was much higher than that mediated by (AL)(6) H(5) K(15) micelles at their respective optimal N/P ratios (3.2 × 10(8) versus 3.9 × 10(7) RLU · mg proteins(-1) ). Therefore, simultaneous delivery of PTX and luciferase-encoding plasmid was conducted using (AF)(6) H(5) K(15) micelles against HepG2 cells, and the results demonstrated that the co-delivery of PTX at 0.01 mg · L(-1) further increased luciferase expression level from 3.2 × 10(8) to 8.0 × 10(8) RLU · mg proteins(-1) at the optimal N/P ratio (i.e., 18). In summary, it is important to optimize the hydrophobic block of the oligopeptide amphiphiles in order to achieve desired properties for co-delivery of drugs and genes.